The pre-clinical evaluation of both adenosine receptor and adenosine uptake site continue to occupy a major portion of the Unit's resources. We have described the complete anatomical distribution of the adenosine uptake site using (3H)dipyridamole autoradiography and shown by these binding experiments that there are multiple populations of brain adenosine uptake sites. Studies measuring adenosine uptake in synaptoneurosomes support the binding and autoradiography. More evidence has been gathered indicating that carbamazepine is acting as an adenosine antagonist. Xanthine-induced seizures have been studied using the new A1-specific antagonist, XAC. Evidence was generated showing that XAC-induced seizures differ form those induced by caffeine in that they are not blocked by RO-15-1788, a benzodiazepine receptor blocker. We have also shown increased adenosine uptake sites in drug resistant human breast cancer cell cultures, suggesting that the adenosine uptake site may be involved in the phenomenon of multi-drug resistance. Recent studies have focused on the role of adenosine agonists as protective agents during cerebral ischemia. The post-ischemic neuropathy is being characterized as it relates to adenosine, glutamate, and benzodiazepine status at both the binding and autoradiographic level. These studies will hopefully assess the potential utility of adenosine agonists in the treatment of stroke patients.